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GENE REGULATION RESULTS IN DIFFERENTIAL GENE EXPRESSION, LEADING TO CELL SPECIALIZATION 3B1.

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Presentation on theme: "GENE REGULATION RESULTS IN DIFFERENTIAL GENE EXPRESSION, LEADING TO CELL SPECIALIZATION 3B1."— Presentation transcript:

1 GENE REGULATION RESULTS IN DIFFERENTIAL GENE EXPRESSION, LEADING TO CELL SPECIALIZATION 3B1

2 2 CONTROL OF GENE EXPRESSION Controlling gene expression is often accomplished by controlling transcription initiation Regulatory proteins bind to DNA May block or stimulate transcription Prokaryotic organisms regulate gene expression in response to their environment Eukaryotic cells regulate gene expression to maintain homeostasis in the organism

3 REGULATORY PROTEINS Gene expression is often controlled by regulatory proteins binding to specific DNA sequences Regulatory proteins gain access to the bases of DNA at the major groove Regulatory proteins possess DNA-binding motifs 3

4 4 PROKARYOTIC REGULATION Control of transcription initiation Positive control – increases frequency of initiation of transcription Activators enhance binding of RNA polymerase to promoter Effector molecules can enhance or decrease Negative control – decreases frequency Repressors bind to operators in DNA Allosterically regulated Respond to effector molecules – enhance or abolish binding to DNA

5 5 Prokaryotic cells often respond to their environment by changes in gene expression Genes involved in the same metabolic pathway are organized in operons Induction – enzymes for a certain pathway are produced in response to a substrate Repression – capable of making an enzyme but does not

6 EUKARYOTIC REGULATION Control of transcription more complex Major differences from prokaryotes Eukaryotes have DNA organized into chromatin Complicates protein-DNA interaction Eukaryotic transcription occurs in nucleus Amount of DNA involved in regulating eukaryotic genes much larger 6

7 TRANSCRIPTION FACTORS General transcription factors Necessary for the assembly of a transcription apparatus and recruitment of RNA polymerase II to a promoter TFIID recognizes TATA box sequences Specific transcription factors Increase the level of transcription in certain cell types or in response to signals 7

8 Before the start of transcription, the transcription Factor II D (TFIID) complex binds to the TATA box in the core promoter of the gene.transcriptionTATA box The TATA box (also called Goldberg-Hogness box ) [1] is a DNA sequence (cis-regulatory element) found in the promoter region of genes in archaea and eukaryotes; [2] approximately 24% of human genes contain a TATA box within the core promoter. [3] [1] DNA sequencecis-regulatory element promoter regionarchaeaeukaryotes [2] [3] Considered to be the core promoter sequence, it is the binding site of either general transcription factors or histones (the binding of a transcription factor blocks the binding of a histone and vice versa) and is involved in the process of transcription by RNA polymerase.transcription factors histonestranscriptionRNA polymerase

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10 10 Promoters form the binding sites for general transcription factors Mediate the binding of RNA polymerase II to the promoter Enhancers are the binding site of the specific transcription factors DNA bends to form loop to position enhancer closer to promoter

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12 12 Coactivators and mediators are also required for the function of transcription factors Bind to transcription factors and bind to other parts of the transcription apparatus Mediators essential to some but not all transcription factors Number of coactivators is small because used with multiple transcription factors

13 TRANSCRIPTION COMPLEX Few general principles Nearly every eukaryotic gene represents a unique case Great flexibility to respond to many signals Virtually all genes that are transcribed by RNA polymerase II need the same suite of general factors to assemble an initiation complex 13

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15 15 EUKARYOTIC CHROMATIN STRUCTURE Structure is directly related to the control of gene expression DNA wound around histone proteins to form nucleosomes Nucleosomes may block access to promoter Histones can be modified to result in greater condensation

16 Methylation once thought to play a major role in gene regulation Many inactive mammalian genes are methylated Lesser role in blocking accidental transcription of genes turned off Histones can be modified Correlated with active versus inactive regions of chromatin Can be methylated – found in inactive regions Can be acetylated – found in active regions 16

17 Some coactivators have been shown to be histone acetylases Transcription is increased by removing higher order chromatin structure that would prevent transcription “Histone code” postulated to underlie the control of chromatin structure 17

18 Chromatin-remodeling complexes Large complex of proteins Modify histones and DNA Also change chromatin structure ATP-dependent chromatin remodeling factors Function as molecular motors Catalyze 4 different changes in DNA/histone binding Make DNA more accessible to regulatory proteins 18

19 19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. Nucleosome sliding 2. Remodeled nucleosome 3. Nucleosome displacement4. Histone replacement ADP + ATP PiPi ATP -dependent remodeling factor

20 20 POSTTRANSCRIPTIONAL REGULATION Control of gene expression usually involves the control of transcription initiation Gene expression can be controlled after transcription with Small RNAs miRNA and siRNA Alternative splicing RNA editing mRNA degradation

21 21 MICRO RNA OR MIRNA Production of a functional miRNA begins in the nucleus Ends in the cytoplasm with a ~22 nt RNA that functions to repress gene expression miRNA loaded into RNA induced silencing complex (RISC) RISC is targeted to repress the expression of genes based on sequence complementarity to the miRNA

22 22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cytoplasm RNA Polymerase II microRNA gene Pri-microRNA Nucleus Drosha Exportin 5 Pre-microRNA Dicer Mature miRNA RISC mRNA RISC mRNA cleavage mRNA RISC Inhibition of translation RNA Polymerase II microRNA gene Pri-microRNA Nucleus Drosha Exportin 5 Pre-microRNA

23 23 PROTEIN DEGRADATION Proteins are produced and degraded continually in the cell Lysosomes house proteases for nonspecific protein digestion Proteins marked specifically for destruction with ubiquitin Degradation of proteins marked with ubiquitin occurs at the proteasome


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